A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.
A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.
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RAB27A 基因的一个常见变异与成人呼出一氧化氮分数相关。
DOI：
10.1111/cea.12461
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
Early Genetics Lifecourse Epidemiology (EAGLE) Consortium
中科院分区：
文献类型：
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作者：
Bouzigon E;Nadif R;Thompson EE;Concas MP;Kuldanek S;Du G;Brossard M;Lavielle N;Sarnowski C;Vaysse A;Dessen P;van der Valk RJ;Duijts L;Henderson AJ;Jaddoe VW;de Jongste JC;GABRIEL consortium;Casula S;Biino G;Dizier MH;Pin I;Matran R;Lathrop M;Pirastu M;Demenais F;Ober C;Early Genetics Lifecourse Epidemiology (EAGLE) Consortium
呼出的一氧化氮（FeNO）是哮喘患者气道嗜酸性粒细胞炎症和对皮质类固醇反应性的生物标志物。我们试图在成人中确定呼出气一氧化氮（FeNO）水平的遗传决定因素，并评估环境和疾病相关因素是否影响这些关联。我们通过对欧洲血统的两个独立发现样本进行荟萃分析，对FeNO进行了全基因组关联研究：远交EGEA研究（法国哮喘遗传学和环境流行病学研究，N=610名成年人）和Hutterites（N=601名成年人），一个生活在公共农场的创始人群体。在撒丁岛一个孤立村庄的成年人中评估了主要结果的重复性（Talana研究，N=450）。然后，我们调查了哮喘、特应性和烟草烟雾暴露对这些遗传关联的影响，以及它们是否也与EAGLE（EArly遗传学和生命过程流行病学，N= 8，858）财团儿童的FeNO值相关。我们检测到与FeNO相关的RAB 27 A（rs 2444043）中的一个常见变异，该变异在合并的发现和复制成人数据集中达到全基因组显著水平（P=1.6×10−7）。该SNP属于RAS癌基因家族成员（RAB 27 A），并与哮喘患者淋巴母细胞系中RAB 27 A的表达数量性状位点相关。第二个提示位点（rs 2194437，P=8.9×10−7）位于钠/钙交换器1（SLC 8A 1）附近，主要在特应性受试者中检测到，并受到吸入性皮质类固醇使用的影响。这两个位点与儿童期FeNO值无关。本研究确定了位于RAB 27 A基因中的一个常见变体，该变体特别影响成人的FeNO水平，并与FeNO水平的调节具有生物学相关性。这项研究为成人FeNO水平的生物学机制提供了新的见解。
Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N=610 adults) and the Hutterites (N=601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N=450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N=8,858) consortium. We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P=1.6×10−7) in the combined discovery and replication adult datasets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P=8.9×10−7) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.
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影响因子：
--
作者：
Kathiresan S;Manning AK;Demissie S;D'Agostino RB;Surti A;Guiducci C;Gianniny L;Burtt NP;Melander O;Orho-Melander M;Arnett DK;Peloso GM;Ordovas JM;Cupples LA
通讯作者：
Cupples LA
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
5.5
作者：
Bolasco, Giulia;Tracey-White, Dhani C.;Hume, Alistair N.
通讯作者：
Hume, Alistair N.
影响因子：
5.9
作者：
Nadif, Rachel;Matran, Regis;Pin, Isabelle
通讯作者：
Pin, Isabelle
DOI：
10.1164/rrcm.2061014
发表时间：
2006-04-01
影响因子：
24.7
作者：
通讯作者：
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